Studies give credence to fecal DNA analysis. (Possible Role in Colorectal Screening).

CHIGAGO -- Two studies have demonstrated the feasibility of using fecal DNA analysis to detect mutations in the gene that initiates colorectal tumors and to detect proximal colorectal cancers.

The studies used a novel approach to detect gene mutations in fecal DNA and demonstrated a high level of specificity. One practical application of these results is the combination of fecal DNA analysis with sigmoidoscopy, which could provide a new approach for the early detection of colorectal neoplasms.

Fecal occult blood tests are noninvasive and thus could enhance patient compliance, but they yield a relatively high rate of false positives. Fecal occult blood is an indirect marker for neoplasia, whereas mutations in oncogenes and tumor suppressor genes are directly associated with neoplastic growth.

Several groups have detected mutations in cancer-related genes in the stool of colorectal cancer patients, but sensitivity and specificity levels were limited by either technical difficulties or low frequencies of mutations in any specific gene.

In an attempt to develop a single gene-based test that would help detect clinically significant, but premetastatic colorectal tumors, researchers at Johns Hopkins University, Baltimore, turned to the adenomatous polyposis coli (APC) gene. Mutations in this gene generally initiate colorectal neoplasia and are relatively easy to detect in tumors, where they are present in every neoplastic cell.

But finding APC mutations in fecal DNA, where they may be present in less than 1 in a 100 of the total APC genes present in the sample, is nothing short of a "miraculous discovery," commented Dr. Bernard Levin, the Betty B. Marcus Chair in Cancer Prevention and professor of medicine at the University of Texas MD Anderson Cancer Center, Houston. Dr. Levin and his colleagues directed the clinical aspects of the study.

Dr. Levin, who presented the results at the annual meeting of the American Society of Colon and Rectal Surgeons, credited the discovery to study coauthors Dr. Bert Vogelstein and Dr. Giovanni Traverso, who led the research team at Johns Hopkins.